PROJECT SUMMARY/ABSTRACT The goal of this competing renewal is to evaluate impacts of two `naturally occurring' interventions - community empowerment (CE) and changes in policing practices - on incidence of HIV/STIs, overdose (OD), and engagement with addiction services among street and indoor sex workers (SWs) in an urban Canadian setting. Currently, there is a lack of research on integrated interventions to address co-occurring harms related to HIV/STI and overdose epidemics, particularly among sex workers, who face disproportionate HIV and STI burdens and severe gaps in access to evidence-based addiction services. While structural and system-level interventions such as CE and changes in policing practices have strong potential to mitigate harms associated with overlapping HIV/STI and overdose epidemics, there remains a scarcity of data on how the implementation of such interventions impacts HIV/STI and overdose incidence and engagement with addiction services among sex workers. Beginning in 2018, a novel CE intervention was launched in Metro Vancouver, British Columbia comprised of: peer navigation; peer-delivered naloxone and point-of-care (POC) HIV/STI screening; and system-level healthcare provider sensitivity training. In response to high rates of violence against SWs and SW advocacy efforts, two Metro Vancouver policing jurisdictions are currently implementing new guidelines for non-harassment and arrest of SWs. Both `naturally occurring' structural and system-level interventions provide a timely opportunity to evaluate their individual and combined effects. Through an R01, our team has recruited and followed a cohort of >800 street and off-street women SWs in Metro Vancouver since 2010, among whom incidence of HIV/STIs and non-fatal OD remain alarmingly high. We propose to take advantage of the rare opportunity to evaluate `naturally-occurring' CE and local policing interventions by addressing the following aims prospectively amongst SWs in Metro Vancouver: (1) Examine the effects of a combination CE intervention on HIV/STI and OD incidence and engagement with OD prevention and services; (2) Evaluate the feasibility, acceptability, and implementation of peer-based HIV/STI point-of-care (POC) screening on HIV/STI incidence and linkage to addiction treatment; (3) Measure impacts of new police enforcement practices on use of addiction services and incidence of HIV/STIs and overdose, including potential differences pre/post CE implementation; (4) Evaluate combined effects of exposure to structural and system-level CE and policing interventions on HIV/STI and OD incidence. To achieve these aims, we will continue to follow and replenish the AESHA cohort of 800 HIV-seronegative women SWs, which is the only ongoing longitudinal SW cohort in North America. Data collection will include semi-annual questionnaires, HIV/STI serology, and administrative linkages to external policing and mortality databases. Amidst syndemics of HIV/STIs, opioid use, and OD among SWs and PWUD in North America, this study will inform combination interventions to reduce the incidence of HIV/STIs and OD amongst marginalized populations.